DFT calculations have been used to investigate the conformational landscape of a library of 1,3-bis[oxo/thioxo-thiazolinyl] aromatic compounds with two stereogenic Csp2-Nsp2 axes (63 compounds). The good correlation between the experimental and DFT-calculated rotational barriers for five of these compounds allowed the use of DFT as a predictive tool for the entire library. The library was generated by systematically varying the position and number of methyl substituents on the central aromatic ring and on the two oxo/thioxo-thiazoline rings. The predicted rotational barriers span from 3 to 58 kcal/mol at 298.15 K, placing these structures across all three categories defined by LaPlante's classification of rotational stereoisomers. DFT calculations unveiled the preferred rotational pathways, highlighting the main factors influencing the energetic cost of the rotation: intramolecular donor-acceptor interactions, ring distortions, and the nature of the exocyclic heteroatom of the thiazoline rings. The structure-rotational barrier relationship obtained for these molecules with two C-N stereogenic axes represents reference values for the design of atropisomers with aryl-thiazoline scaffolds for various applications, such as chiral bioactive compounds. Also, 15N NMR data are reported for some of the synthesized compounds.

Nontargeted metabolite profiling prioritizes robust comparisons of the analytical outcomes rather than absolute concentration measurement. In this work, it is shown that a harmonized 1D 1H NMR workflow, originally adopted for nontargeted NMR analysis, can also support reliable quantitative determination of betaine when spectra acquired under profiling-oriented conditions, nonideal for quantification, are anchored to gravimetrically traceable standards and corrected by a suitable factor accounting for bias in absolute concentration estimates. This study presents the results of an interlaboratory comparison designed to investigate the main factors affecting the accuracy and reproducibility of nontargeted 1H NMR data when different spectrometers and operators are involved. The case study focused on the determination of betaine in aqueous extracts of durum wheat (cvs. Marco Aurelio and Iride) and the corresponding pasta products. A common set of samples was analyzed using a harmonized acquisition protocol across 50 spectrometers operating at magnetic field strengths ranging from 80 to 700 MHz. Two data-processing strategies were compared: operator-dependent processing (multiple operators using different software packages) and centralized processing (single operator) performed with five different software platforms. Quantification was carried out by both an internal standard method, using 3-(trimethylsilyl)-2,2,3,3-tetradeutero-propionic acid, sodium salt (TSP-d 4) as a reference, and an external standard method, employing TSP-d 4, dimethyl sulfone (DMSO2), and betaine as references. The results demonstrated that the largest source of variability lies in operator-dependent data-processing choices rather than instrumental characteristics. TSP-d 4 systematically overestimated the betaine concentration and introduced additional variability. By contrast, DMSO2 and betaine provided accurate and highly precise quantification with Horwitz ratios consistently below unity, indicating reproducibility superior to generic interlaboratory expectations. Internal standard method also achieved reproducibility within the accepted 0.5-2.0 HorRat range. Overall, this work shows that spectra acquired for nontargeted metabolite profiling can support quantitative determination of betaine, and potentially of other selected metabolites, provided that the same acquisition and processing protocol is maintained and that appropriate gravimetrically traceable calibration is applied.

Conic projection as manifold enable calculation dihedral θHnHn+1[deg] angles from differences between two atoms of carbon ΔδCnCn+1[ppm] in three steps or from only one atom of carbon δCn[ppm] in close relationships with tetrahedral φCn[deg] angles under 3-Sphere approach. Hopf fibration and Lie algebra ensuring calculation dihedral θHnHn+1[deg] angles from vicinal ϕ[deg] angle, angle results from vicinal coupling constant 3JHH[Hz]. Real Hopf fibration for calculation dihedral θHnHn+1[deg] angle in real space, and R16 octonionic Hopf fibration, double of quaternionic R7, for all cis, trans-ee, trans-aa stereochemistry, unreal space relative to calculated dihedral θHnHn+1[deg] angle. Continue “deformation”, homotopic behaviour h ⇆ h-1 characteristic for wave NMR data, probably a point of swich on Möbius band, in case of radius r of the cone inscribes on sphere at tangent point, calculated from height of cone h or inverse of height h-1, the tan function of h is equal with sin function of h-1. Dihedral θHnHn+1[deg] and tetrahedral φCn[deg] angles are from the trigonometric point of view under sin and tan function, or viceversa, homotopic behavior of NMR data under conic projection demonstrating that. Because the dihedral θHnHn+1[deg] angles are not found in first unit, for few vicinal coupling constants 3JHH[Hz], the rule accepted until now are explored taking in consideration other sets for building unit along the set C, respectively D, E and F, G, or vicinal angle ϕ[deg] with its three possible dihedral θHnHn+1[deg] angles in close relationships with tetrahedral φCn[deg] angles under seven sets unit. Building units through sets U or S calculated from sin or tan functions until calculated angles are almost equals with angles of unit U1 or S1, required long time for calculation.

A p-phenylenediamine-catechol-based oligomer was synthesized via oxidative polycondensation in an acidic medium under ultrasonic irradiation, employing potassium persulfate as the oxidant to obtain an oligomeric material. The resulting material was characterized by Fourier-transform infrared (FT-IR) spectroscopy, ultraviolet-visible (UV-Vis) spectroscopy, thermogravimetric analysis (TGA), nuclear magnetic resonance (NMR) spectroscopy, scanning electron microscopy (SEM), X-ray diffraction, and electron spin resonance (ESR) spectroscopy. FT-IR and NMR analyses confirm that the reaction conditions (with and without surfactant, in presence of ethanol) significantly affect the composition of the resulting materials. It was established that, depending on the reaction conditions, the formation of a trimer composed of two para-phenylenediamine units and one catechol moiety, as well as the formation of poly-1,2-dihydroxybenzene, occurs in different ratios. No products of the individual polycondensation of p-phenylenediamine were detected. UV-Vis spectroscopy indicates wide-band-gap semiconducting behavior, with an optical band gap of approximately 4.7 eV estimated from the Tauc plot analysis. TGA shows the oligomer is stable up to similar to 270 degrees C. SEM revealed an irregular, predominantly flake-like fragmented surface morphology without well-defined individual particles. ESR confirmed unpaired electrons within the oligomer structure. Temperature-dependent conductivity measurements revealed an unusual conductivity trend, where conductivity slightly increased with decreasing temperature within the investigated range. At room temperature, the measured conductivity is 1.06 & times; 10(-7) S/cm.

The paper explores the information provided by various magnetic resonance (MR) techniques in the diagnosis of galactosemia. Galactosemia (GA) is an autosomal recessive inborn error of metabolism, included in the category disorders of carbohydrate metabolism. In this disorder, the body is unable to metabolize galactose, leading to the accumulation of toxic intermediates like galactose-1-phosphate, galactitol, and galactonate. The information provided by magnetic resonance imaging (MRI), localized nuclear magnetic resonance spectroscopy (MRS), and non-localized nuclear magnetic resonance (NMR) is complementary both in terms of data supplied and organ/body fluid targeted. In spite of this complementarity, we found that these MR techniques have never been jointly applied in the diagnosis of GA.

Novel pyrrolo[1,2-a]benzimidazoles and pyrrolo[1,2-a]quinoxalines bearing a nitro group on the pyrrole ring were synthesized via one-pot multicomponent reactions of 1-substituted benzimidazoles with dimethyl acetylenedicarboxylate and bromonitromethane. All synthesized compounds were structurally characterized by IR, NMR and HRMS spectroscopy.

Although both localized nuclear magnetic resonance spectroscopy (MRS) and non-localized nuclear magnetic resonance spectroscopy (NMR) generate the same information, i.e., spectra generated by various groups from the structure of metabolites, they are rarely employed in the same study or by the same research group. As our review reveals, these techniques have never been applied in the same study of methylmalonic acidemia (MMA), propionic acidemia (PA) or vitamin B12 deficiency patients. On the other hand, MRS and NMR provide complementary information which is very valuable in the assessment of the severity of disease and efficiency of its treatment. Thus, MRS provides intracellular metabolic information from localized regions of the brain, while NMR provides extracellular metabolic information from biological fluids like urine, blood or cerebrospinal fluid. This paper presents an up-to-date review of the NMR and MRS studies reported to date for methylmalonic and propionic acidemias. Vitamin B12 deficiency, although in most of its cases not inherited, shares similarities in its metabolic effects with MMA and it is also covered in this review.

Strigolactones (SLs) have potential to be used in sustainable agriculture to mitigate various stresses that plants have to deal with. The natural SLs, as well as the synthetic analogs, are difficult to obtain in sufficient amounts for practical applications. At the same time, fluorescent SLs would be useful for the mechanistic understanding of their effects based on bio-imaging or spectroscopic techniques. In this study, new fluorescent SL mimics containing a substituted 1,8-naphthalimide ring system connected through an ether link to a bioactive furan-2-one moiety were prepared. The structural, spectroscopic, and biological activity of the new SL mimics on phytopathogens were investigated and compared with previously synthetized fluorescent SL mimics. The chemical group at the C-6 position of the naphthalimide ring influences the fluorescence parameters. All SL mimics showed effects similar to GR24 on phytopathogens, indicating their suitability for practical applications. The pattern of the biological activity depended on the fungal species, SL mimic and concentration, and hyphal order. This dependence is probably related to the specificity of each fungal receptor–SL mimic interaction, which will have to be analyzed in-depth. Based on the biological properties and spectroscopic particularities, one SL mimic could be a good candidate for microscopic and spectroscopic investigations.

Background: kidney transplant recipients are exposed to multiple pathogenic pathways that may alter short and long-term allograft survival. Metabolomic profiling is useful for detecting potential biomarkers of kidney disease with a predictive capacity. This field is still under development in kidney transplantation and metabolome analysis is faced with analytical challenges. We performed a cross-sectional study including stable kidney transplant patients and aimed to search for relevant associations between baseline plasmatic and urinary metabolites and relevant outcomes over a follow-up period of 3 years. Methods: we performed a cross-sectional study including 72 stable kidney transplant patients with stored plasmatic and urinary samples at the baseline evaluation which were there analyzed by nuclear magnetic resonance in order to quantify and describe metabolites. We performed a 3-year follow-up and searched for relevant associations between renal failure outcomes and baseline metabolites. Between-group comparisons were made after classification by observed estimated glomerular filtration rate slope during the follow-up: positive slope and negative slope. Results: The mean estimated GFR (glomerular filtration rate) was higher at baseline in the patients who exhibited a negative slope during the follow-up (63.4 mL/min/1.73 m2 vs. 55.8 mL/min/1.73 m2, p = 0,019). After log transformation and division by urinary creatinine, urinary dimethylamine (3.63 vs. 3.16, p = 0.027), hippuric acid (7.33 vs. 6.29, p = 0.041), and acetone (1.88 vs. 1, p = 0.023) exhibited higher concentrations in patients with a negative GFR slope when compared to patients with a positive GFR slope. By computing a linear regression, a significant low-strength regression equation between the log 2 transformed plasmatic level of glycine and the estimated glomerular filtration rate was found (F (1,70) = 5.15, p = 0.026), with an R2 of 0.069. Several metabolites were correlated positively with hand grip strength (plasmatic tyrosine with r = 0.336 and p = 0.005 and plasmatic leucine with r = 0.371 and p = 0.002). Other urinary metabolites were found to be correlated negatively with hand grip strength (dimethylamine with r = -0.250 and p = 0.04, citric acid with r = -0.296 and p = 0.014, formic acid with r = -0.349 and p = 0.004, and glycine with r = -0.306 and p = 0.01). Conclusions: some metabolites had different concentrations compared to kidney transplant patients with negative and positive slopes, and significant correlations were found between hand grip strength and urinary and plasmatic metabolites.

Gene therapy is one of the most potential therapeutic approaches in direct and specific regulation of biological functions of macrophages at the gene level for efficient cell therapy. However, the delivery of genetic material to macrophages is extremely challenging, because of low stability, specificity and inability of therapeutic genes to efficiently enter the cells. Here, we present a method that uses the hybrid electrospun architectures based on gelatin-alginate decorated with carboxylated graphene oxide (HAG/G) as efficient substrate for loading and in vitro local and controlled delivery of plasmid DNA (pDNA) to macrophages as an alternative to systemic gene delivery carriers. Polyethyleneimine (PEI) is employed to assemble PEI/pDNA nanoparticles (Np) - used as model of carrier. The dispersion of GO-COOH sheets shifts the surface zeta potential of HAG/G to high negative value (SZP = -16.8 ± 2.21 mV) and further increases the encapsulation efficiency of PEI/pDNA Np onto hybrid HAG/G electrospun architectures to ∼ 69 % (HAG/G-Np). The in vitro biological investigations show a good metabolic activity of macrophages seeded onto HAG/G-Np (MTT assay), while gene expression experiments (fluorescent microscopy) show a 30 % increase in transient gene transfection of cells cultured in the presence of HAG/G-Np as compared to those incubated with free PEI/pDNA Np.

The poor water solubility of natural antioxidants restricts their bioavailability and therapeutic use. We aimed to develop a new phytosome formulation with active compounds from extracts of ginger (GINex) and rosehips (ROSAex) designed to increase their bioavailability, antioxidant and anti-inflammatory properties. The phytosomes (PHYTOGINROSA-PGR) were prepared from freeze-dried GINex, ROSAex and phosphatidylcholine (PC) in different mass ratios using the thin-layer hydration method. PGR was characterized for structure, size, zeta potential, and encapsulation efficiency. Results showed that PGR comprises several different populations of particles, their size increasing with ROSAex concentration, having a zeta potential of ~-21mV. The encapsulation efficiency of 6-gingerol and β-carotene was >80%. 31P NMR spectra showed that the shielding effect of the phosphorus atom in PC is proportional to the amount of ROSAex in PGR. PGR with a mass ratio GINex:ROSAex:PC-0.5:0.5:1 had the most effective antioxidant and anti-inflammatory effects in cultured human enterocytes. PGR-0.5:0.5:1 bioavailability and biodistribution were assessed in C57Bl/6J mice, and their antioxidant and anti-inflammatory effects were evaluated after administration by gavage to C57Bl/6J mice prior to LPS-induced systemic inflammation. Compared to extracts, PGR induced a 2.6-fold increase in 6-gingerol levels in plasma and over 40% in the liver and kidneys, in parallel with a 65% decrease in the stomach. PGR treatment of mice with systemic inflammation increased the sera antioxidant enzymes paraoxonase-1 and superoxide dismutase-2 and decreased the proinflammatory TNFα and IL-1β levels in the liver and small intestine. No toxicity was induced by PGR either in vitro or in vivo. In conclusion, the phytosome formulation of GINex and ROSAex we developed resulted in stable complexes for oral administration with increased bioavailability, antioxidant and anti-inflammatory potential of their active compounds.

Binary halogen-bonded co-crystals with interesting supramolecular architectures are formed using two types of azulenyl compounds as halogen-bond acceptors and perfluorinated di- and triiodobenzenes as donors.

Solid activators based on waste glass for the manufacture of one-part alkali-activated fly ash/red mud materials were synthesized, characterized, and tested in this work. The synthesis was carried out via alkaline fusion with sodium hydroxide at different reaction temperatures and at different sodium hydroxide/waste glass mass ratios. The results showed that the reaction temperature decisively influences the properties of the obtained solid activators. Thus, the best results regarding the water solubility of solid activators were obtained for the synthesis temperature of 600 °C, regardless of the sodium hydroxide/waste glass mass ratio. Also, the use of these assortments of solid activators led to obtaining the best compressive strength of one-part alkali-activated fly ash/red mud materials. The best results were obtained for the solid activator synthesized at a temperature of 600 °C and a sodium hydroxide/glass waste mass ratio of two.

Due to its inherent properties and wide availability, cellulose acetate is an extremely competitive candidate for the production of polymeric membranes. However, for best results in particular applications, membrane modification is required in order to minimize unwanted interactions and introduce novel characteristics to the pristine polymer. In this study, the surface of commercial cellulose acetate membranes was functionalized with 4'-aminobenzo-15-crown-5 ether, using a covalent bonding approach. The main goal was the improvement of the membranes biomineralization ability, thus making them prospective materials for bone regeneration applications. The proposed reaction mechanism was confirmed by XPS and NMR analysis while the presence of the functionalization agents in the membranes structure was showed by ATR FT-IR and Raman spectra. The effects of the functionalization process on the morphology, thermal and mechanical properties of the membranes were studied by SEM, TGA and tensile tests. The obtained results revealed that the cellulose acetate membranes were successfully functionalized with crown ether and provided a good understanding of the interactions that took place between the polymer and the functionalization agents. Moreover, promising results were obtained during the Taguchi biomineralization studies. SEM images, EDX mapping and XRD spectra indicating that the CA-AB15C5 membranes have a superior Ca2+ ions retention ability, this causing an accentuated calcium phosphate deposition on the modified polymeric fibers, compared to the neat CA membrane.

A new triazol-3-one resulted unexpectedly from the reduction reaction of a heterocyclic thioketone using sodium borohydride in pyridine containing a small amount of water. The structure of the new compound was characterised using FT-IR, 1D and 2D NMR, and HRMS spectroscopic methods.

One critical step in new drugs development is the investigation of the interactions between drug candidate and target protein. Nuclear Magnetic Resonance Spectroscopy (NMR) is a well-established technique for studding these interactions.Due to its availability and structural similarities to human albumin, bovine serum albumin (BSA) is widely accepted as a model for investigating the binding of small molecules to serum albumin. We report here on the evaluation of binding interactions between BSA and 18 metabolites using saturation transfer difference (STD) NMR experiments.Positive STD signals that indicate metabolite-protein interactions were obtained for leucine, pyruvic acid, valine, threonine, alanine, 4-aminohippuric acid and tryptophan.

Novel indolizines and pyrrolo[1,2-c]pyrimidines bearing a 3-carbonylchromen-2-one moiety on the pyrrole rings were synthesized and spectroscopic properties of some of synthesized compounds were investigated. Synthetic procedures started from 4-substituted pyrimidines, 3-(2-bromoacetyl)-2H-chromen-2-one and electron-deficient alkynes via 3+2 dipolar cycloaddition of cycloimmoniumylides, generated in situ from their corresponding quaternary salts, in the presence of an epoxide playing the role of acid scavenger and reaction solvent. The structures of novel compounds were confirmed by chemical analyses, IR and NMR spectroscopy. Spectroscopic properties of some of the synthesized compounds were investigated.

Objective: Cardiovascular diseases are the leading cause of death globally, despite significant advances in diagnosis and treatment. Among the multiple already well-known cardiovascular risk factors, hypertension, diabetes mellitus type II and dyslipidaemia are the most frequent and show the best correlations with the risk of further developing a major cardiovascular event. The main objective consists in identifying the potential particularities that diabetes could have on the lipid profile in hypertensive patients, while also discovering bio-markers with a higher potential accuracy of predicting further major cardiovascular events, using NMR spectroscopy. Design and method: We have selected a group of 30 hypertensive patients and a control group of 17 otherwise healthy individuals in order to assess the influence of diabetes on the lipid panel in hypertensive patients. A blood sample of 6 mL was collected before and after meals and 5 types of NMR spectroscopy experiments were performed for each sample. Results: It was noted that the fasten triglycerides levels, VLDL and IDL particle number, apolipoprotein A1, A2, B100 levels, as well as the ratio apolipoprotein B100/apolipoprotein A1 are all potentially useful markers that could be successfully used to differentiate between the strictly hypertensive patients and the ones that associate type II diabetes mellitus. The study also confirmed once more our previous reports that the fasting status upon sampling has little influence on the lipid panel final values. Conclusions: We have evaluated the lipid panel differences induced by diabetes mellitus type II in hypertensive patients and we have compared the results with an otherwise healthy control group. We have identified the NMR spectroscopy markers that could be able to spot subtle differences in the lipid profiles of the two study groups (two hypertensive groups, one consisting in strictly hypertensive patients, the other one including hypertensive patients with already known type II diabetes mellitus), even when LDL levels have been lowered to normal levels due to statin treatment. We have once more concluded that the patient's fasting status has no influence on the final analysis.

The interactions between four native and modified beta-cyclodextrins and a benzimidazolium bromide salt were analyzed through UV-Vis and NMR Spectroscopy. The new benzimidazolium salt was obtained by simple and efficient conversion of N-1 substituted 5,6-dimethylbenzimidazole with phenacyl bromide in acetone. In all cases, the complexes stoichiometry was 1:1, as determined from UV-Vis titrations. Based on the values for association constants, the strength of the interactions with benzimidazolium bromide was weakest with the methyl substituted beta-cyclodextrin and strongest with the sulfobutylether substituted beta-cyclodextrin. Through-space NOE experiments were used to investigate the structural aspects of inclusion process. The obtained NOE correlations indicate coexistence of two inclusion modes: one with the phenacyl group inside the cyclodextrin cavity and the second one with dimethyl-substituted benzene ring inside the cavity. The imidazole ring and the ethyl substituent have been proven to remain outside the cyclodextrin cavity in both inclusion modes.